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Venous thromboembolic disease (VTE) is a frequent clinical problem during pregnancy and post-partum. Pulmonary embolism (PE) remains the most common cause of mortality during pregnancy and post-partum in western countries. In the majority of cases, DVT may be diagnosed by non-invasive tests such as clinical probability, D-dimer measurement and venous compression ultrasonography. In contrast, at least one irradiating invasive exam is necessary in suspected PE. The lung scan, the most validated diagnostic test for PE during pregnancy and fetal irradiation is quite low, in particular if only perfusion lung scan is used. Helical computed tomography (hCT) has widely replaced lung scan in the diagnostic approach of suspected pulmonary embolism. However, it has never been validated in pregnant women.

Patients suffering from chronic obstructive pulmonary disease (COPD) are often admitted to hospital with an exacerbation of their disease that manifests itself with an increase in cough and/or sputum, increased dyspnoea and sometimes chest pain. These episodes are most often attributed to an acute exacerbation of bronchial infection but the real cause is often unknown. COPD is considered a risk factor for pulmonary embolism (PE) and PE is part of the differential diagnosis of an acute exacerbation of COPD. However, the symptoms of these two conditions overlap to a considerable extent and the investigation of PE is often ignored in these patients. Therefore the true prevalence of PE in this situation is unknown. Nevertheless several small series suggest that up to 30% of patients seen as emergencies with exacerbations of COPD may have a deep vein thrombosis or PE. The aims of this study are therefore: 1. To evaluate the prevalence of PE in patients admitted as emergencies with exacerbations of COPD; and 2. To attempt to develop a prediction guide for PE in this population in order to identify the patients in whom PE should be investigated.600 consecutive patients admitted as emergencies with exacerbations of COPD will be included in a cross sectional study in three university hospitals (Geneva and Lausanne in Switzerland, and Amiens in France). Patients fulfilling the inclusion criteria will be investigated by a diagnostic algorithm appropriate for the study of PE, including D-dimer levels and, in those with abnormal results, ultrasonic scan of the deep veins of the legs and spiral CT scan. The patient characteristics on admission will be incorporated in a multivariate regression analysis in an attempt to identify the predictive factors for PE in these patients. The expected duration of the study is 24 months.This study should determine the prevalence of PE in patients admitted as emergencies with exacerbations of COPD and therefore help decide when, and in which patients, a systematic search for PE should be undertaken.

FIBRIN BREAKDOWN PRODUCTS: D-dimers are protein substances resulting from the action of 3 enzymes, thrombin, factor XIII and plasmin, on the fibrinogen molecules. In the case of thrombosis, all these enzymatic reactions are activated, explaining the increase in D-dimer levels induced. The notion of a threshold is only significant for a given test; the 500 micrograms/L threshold is widely used for tests relying on ELISA methods (enzyme-linked immunosorbent assay). FROM A TECHNICAL POINT OF VIEW: The use of D-dimer ELISA in excluding pulmonary embolism is now well established. New quantitative tests with latex, based on a turbidimetric method, also appear interesting in this context. The latter is reliable, rapid, inexpensive, remarkably sensitive (97 to 100%) and widely available.Performed in the initial stages of diagnosis in an out-patient population with a 20-25% prevalence of the disease, it excludes the diagnosis in around 30% of patients. Decisional analysis models have shown that this method is economically profitable. However, in elderly hospitalised patients, its clinical utility is lesser because of its low specificity in this population. The association of high clinical probability of pulmonary embolism and normal D-dimer leves is rare and has a weaker negative predictive value, even when the ELISA technique is used.

Peripheral arterial disease of the lower limbs is a manifestation of atherosclerosis, and may also affect other vascular territories such as the coronary and cerebral arteries. Progressive narrowing of the vessels up to total occlusion can present as intermittent claudication or pain at rest, with or without cutaneous lesions. Patients with intermittent claudication are at a low risk of amputation, and the symptom has to be regarded as a warning signal for myocardial infarction and stroke. Nevertheless, if the patient's walking distance is too limited to allow a near-normal life, symptomatic treatment to improve quality of life should be considered. Treatment may consist of walking exercise, surgical or interventional radiological revascularisation, or, in some cases, administration of vasoactive drugs. Antiplatelet agents should be administered in an attempt to limit disease progression and prevent cardiac and cerebrovascular complications, together with active measures to reduce established risk factors such as smoking, diabetes, hyperlipidaemia, and arterial hypertension. The presence of pain at rest indicates that a lower limb is jeopardised, especially when the criteria for critical ischaemia have also been met. These criteria include the presence of chronic (lasting for more than 2 weeks) symptoms of ischaemia at rest and a systolic blood pressure less than 50 mm Hg or 30 mm Hg at the ankle or big toe, respectively. In such a situation, revascularisation should be attempted whenever possible. If this is not possible or if the procedure has failed, prostacyclin administered intravenously for days or weeks is an alternative. After revascularisation, early reocclusion may be prevented by administering anticoagulants and late reocclusion by antiplatelet agents, in conjunction with eradication of risk factors. In all situations, therapeutic decision-making should be undertaken in a multidisciplinary setting and should include the following: specialists in angiology (an internist) and interventional radiology; a vascular surgeon; an orthopaedic surgeon, if necessary; and diabetes and infectious disease specialists.

The presence of D-dimers in the serum reflects fibrin formation and lysis. If the serum D-dimer level is lower than a threshold level which depends on the assay technique (usually 500 micrograms/l), pulmonary embolism can be excluded with a predictive value of 95%. This makes D-dimer assay an ideal screening tool for ambulatory patients with suspected pulmonary embolism. Screening costs can be reduced in about one-third of the cases as other tests are not required. For routine practice, only ELISA tests have been validated for this indication, the sensitivity of latex tests being too low. D-dimer assay would be of little benefit for patients hospitalized for more than 24 for reasons other than suspected pulmonary embolism as specificity is very low in this population.

The presence of D-dimers in the bloodstream is secondary to fibrin formation and lysis. Because fibrin is the main component of a thrombus, deep vein thrombosis and/or pulmonary embolism may be excluded with a predictive value of more than 95%, provided D-dimer plasma concentration is below a critical, assay-dependent cutoff. The D-dimer test is thus an ideal screening step in outpatients clinically suspected of venous thromboembolism. Only ELISA tests have been validated in clinical practice at present time for this indication, sensitivity of latex assays being insufficient.

Antithrombotic agents are frequently used in patients with peripheral arterial occlusive disease. This use is based on controlled clinical trials but also (mainly) on empirical experience of clinicians or on extrapolation from data obtained in coronary patients. The present paper reviews briefly the indications of anti-platelet and anticoagulant treatments in the settings of primary prevention, and secondary prevention in chronic or acute arterial insufficiency of lower limbs, after revascularization surgery, and following angioplastic procedures. Many recommendations are derived from corresponding situations in the coronary setting although analogies are not always pertinent. In summary, aspirin is indicated in almost all patients with peripheral arterial occlusive disease, at least for preventing acute coronary or cerebrovascular events. Heparin is used (or even indicated) during vascular surgical or interventional radiologic procedures. The place of oral anticoagulants is less well established, except after an acute arterial obstruction from an embolus of cardiac origin. Nonetheless, they are frequently prescribed after distal bypasses (below the knee) or in case of poor run-off.

The estrogen component of oral contraceptives enhances both coagulation and fibrinolysis. These contradictory effects result in activation of coagulation and an increased risk of venous thromboembolism. The relative risk is about 4-fold as compared with a nonuser of the same age. However, the risk of deep vein thrombosis or pulmonary embolism attributable to the pill is small (2 cases per 10,000 users per year). Pills containing a progestagen of the so-called 3rd generation seem to increase the risk by an additional factor of 2. Though small, the risk of venous thromboembolism makes it necessary before any oral contraceptive prescription to take a thorough personal and family history (including risk factors) and to study the risk-benefit ratio on an individual basis. Moreover, patients should receive detailed information on the evaluation. Postmenopausal hormone replacement therapy does not induce significant hemostatic changes (especially with transdermal application) and is not associated with a proven risk of venous thromboembolism. Venous risk factors thus do not contraindicate the use of hormone replacement therapy, except perhaps in the immediate (one-year?) period after an acute event.

The diagnostic strategy of pulmonary embolism is based firstly on pulmonary scintigraphy, a non-invasive investigation which provides a definitive diagnosis in about 30% of patients, and then on pulmonary angiography, which remains the investigation of reference. However, new diagnostic methods have been introduced in order to reduce the number of angiographies. Measurement of plasma D-dimer, a fibrin degradation product, enables exclusion of the diagnosis in 20-50% of patients without pulmonary embolism when the result is normal on ELISA (500 micrograms/l with the commercialized Stago test). This is due to the very high sensitivity of D-dimer: in a compilation of recent series with a total of 1,159 patients suspected of having pulmonary embolism, their concentration was over the threshold of 500 micrograms/l in 96% (CI 95%, 93-98) of patients with pulmonary embolism. On the other hand, their low specificity makes them useless for a positive diagnosis of the condition. Lower limb venous compression ultrasonography enables detection of proximal deep venous thrombosis in about 57% (CI 95%, 52-62) of patients with pulmonary embolism, posing the indication for anticoagulation without further investigations because of its high specificity (98%) (CI 95%, 97-99). When venous ultrasonography is normal, however, pulmonary embolism cannot be excluded. A diagnostic strategy associating these two investigations and pulmonary scintigraphy reduces the number of diagnostic angiographies by 30 to 50% according to whether D-dimer and ultrasonography are performed before or after scintigraphy respectively. More extensive use of D-dimer in clinical practice requires more rapid and equally reliable unitary tests as the ELISA.

Severe (reduction of vessel diameter by more than 70%) asymptomatic carotid artery stenosis is associated with a risk of cerebrovascular accident of 2-5% in the year following diagnosis. Results of large, prospective, randomized studies suggest that prophylactic carotid endarterectomy may be beneficial in this situation. However, the elements that must be taken into consideration before deciding to operate on an individual patient are extremely complex. Age and comorbidity (especially cardiovascular conditions) must be considered, as well as perioperative risk and expected medium- and long-term benefits, as compared with optimal conservative treatment. Decision analysis may be of considerable help in such a complex situation by considering objectively and explicitly all these epidemiologic and individual variables. Specifically, the technique makes it possible to simulate threshold probabilities of perioperative complications above which the risks of prophylactic endarterectomy outweigh its benefit, expressed as 5-year survival free of cerebrovascular event. These thresholds are 4%, 3% and 2% for a patient aged 65, 75 and 85 respectively. If 2-year event-free survival is considered, the surgical risk should not exceed 1.5% for a patient aged 65 years or 1% above that age. This type of analysis makes it possible to individualize the guidelines of international panels of experts, but ultimately the decision to operate or not must also consider the psychological profile of the patient and his attitude towards risk ("risk-seeking or risk-averse").

Anticoagulants (unfractionated heparin UFH, low-molecular-weight heparins LMWH, coumarins) are mainly used to prevent (prophylactic dosage) or treat (therapeutic dosage) deep-vein thrombosis and pulmonary embolism. After surgery, prophylactic regimens of UFH and LMWH induce a doubling of the hemorrhagic risk which is observed under placebo. At therapeutic dosages, UFH and LMWH are associated with a risk of major bleeding of about 5%, with a trend favouring LMWH for a similar antithrombotic efficacy. At therapeutic levels, coumarins induce major bleeding at a rate of approximately 1%/month. This figure is proportional to the duration and the intensity (INR) of the treatment. It appears to be the major determinant of an optimal duration of anticoagulant treatment following deep-vein thrombosis.

Plasma measurement of D-dimers (DD) with the Elisa technique is very useful in the diagnostic approach of venous thromboembolic diseases: a low level of plasma D-dimers (500 micrograms/l when using the Elisa from Stago) allows to exclude the diagnosis of deep venous thrombosis or pulmonary embolism with predictive values of 94% and 98%, respectively. Such a diagnostic potential is particularly useful in the group of patients with inconclusive perfusion-ventilation scintigraphy (low or indeterminate probability of pulmonary embolism) which represent more than 50% of the patients with suspected pulmonary embolism. Presence of pulmonary embolism is suggested by levels above 4.000 micrograms/l in the collective of outpatients who are urgently referred because of clinical suspicion of embolism.

The indications, contraindications, results and complications of thrombolytic treatment in pulmonary embolism are reviewed. The natural history of this condition and recent developments in the field of thrombolysis are particularly emphasized. If hemodynamic breakdown is present, thrombolysis is clearly indicated. On the other hand, the place of thrombolytic treatment in the presence of non-massive pulmonary embolism remains to be established. In practice the authors' policy includes intravenous administration of a rather high dose of rt-PA (alteplase) (50 mg) over a short period of time (2 hours), possibly followed by a second 5-hours infusion of 10 mg/h. However, other treatment schemes are also well established.

Low-molecular weight heparin (LMWH) fractions have progressively replaced standard heparin for the prevention of postoperative deep venous thrombosis (DVT). The improved bioavailability and increased half-life of these fragments allowed indeed to prevent DVT while using one single daily subcutaneous injection instead of two or three with standard heparin, a clear-cut advantage both for the patient and the nurse. In the treatment of established DVT, the presently available data suggest that these fractions, administered in 2 daily subcutaneous injections, are equivalent to standard heparin with regard to the effects on the phlebogram and to the risk of major bleeding. However, there are no definitive data on the prevention of pulmonary embolism which is the primary aim of anticoagulant treatment in established DVT, there is no clear-cut advantage for the LMWH fractions in this indication, except if laboratory control can be omitted, which is still matter of debate.

Plasma measurement of D-dimers (DD), which are fibrin-specific degradation products, progressively replaces the cumbersome dosage of fibrinogen degradation products (FDP's) in serum for diagnosis and follow-up of consumption coagulopathies, for diagnosis of prethrombotic states and, potentially, for the control of the efficacy of antithrombotic therapies. Moreover, when the ELISA technique is used, this measurement may be very useful in the diagnosis approach of venous thromboembolic disease. In the present review, data are presented which strongly support the view that a low level of plasma D-dimers (less than 500 micrograms/L when using the ELISA from Stago) allows to exclude the diagnosis of deep venous thrombosis or pulmonary embolism with predictive values of 94 % and 100 % respectively. It is suggested that such a diagnostic potential might be very useful in the group of patients with inconclusive perfusion-ventilation scintigraphy (low or indeterminate probability of pulmonary embolism) which represent about 50 % of the patients with suspected pulmonary embolism.

Deep venous thrombosis and pulmonary embolism are frequent complications of surgery. A careful evaluation of both the thromboembolic and the haemorrhagic risks depends on the type of intervention and associated individual risk factors. Such an evaluation should allow allocating the patient to an appropriate prevention which consists of mechanical and/or pharmacological means.Deep venous thrombosis and its complication pulmonary embolism are responsible for more than 50,000 deaths annually in the US, 2/3 of which occur postoperatively. Nearly 75% of such deaths could be avoided by adequate prophylaxis. All forms of surgery entail some risk of deep venous thrombosis, ranging from 10% after endoscopic prostate resection to over 50% for total hip replacement. 1.6 of thromboses will embolize and 1/4 of pulmonary emboli are fatal. The goal of prevention is to decrease the incidence of fatal pulmonary emboli while limiting the risks related to prevention. A secondary goal is to reduce the frequency of postthrombotic syndrome, a late complication of deep venous thrombosis which frequently causes invalidism. A preoperative evaluation of risks of deep venous thrombosis and of the likelihood of bleeding problems should be followed by selection of appropriate preventive measures. The evaluation should be repeated postoperatively, taking into account such factors as the duration of the intervention, the diagnosis, and the predicted duration of bed rest. Evaluation of the risk of deep venous thrombosis requires knowledge of its etiopathogenesis. Deep venous thrombosis results from a multifactorial process involving venous stasis, lesion of the vascular wall, and anomalies of blood composition. All the clinical risk factors for deep venous thrombosis are related to 1 or more of these elements. Risk factors related to stasis include immobilization, postoperative or postpartum status, pregnancy, and Cockett's syndrome. Risk factors related to lesions of the vascular wall include hip surgery, trauma, age, sepsis, varices and obesity, and postthrombotic syndrome. Risk factors related to blood anomaly include postoperative status, pregnancy, oral contraceptive use, cancer, nephrotic syndrome, hypercoagulability, trauma, and heredity. The most common clinical risk factors for deep venous thrombosis are age, surgical intervention, trauma, burns, cancer, pregnancy and delivery, oral contraceptive use, varices, obesity, and postthrombotic syndrome. The relative risk of deep venous thrombosis among OC users is 4.0 overall and higher for those with type A blood. The pathogenic mechanisms are similar to those of pregnancy except that the fibrinolytic capacity is not change. The principal mechanism is perhaps the declining level of antithrombin III, observed with estrogens and some progestins. Among methods of prevention are different forms of compression, use of heparin alone or in combination with other drugs, and oral anticoagulants.

Intracoronary infusions of streptokinase result in recanalization in about 80% of patients treated during the 4 hours following the first symptoms of myocardial infarction. With short, high dose intravenous infusions (streptokinase 1,500,000 units in 30 min) the recanalization rate is of the order of 60-75%. The high dose of streptokinase is well tolerated, and the intravenous infusion presents the advantage of shortening by about 2 hours the delay required to start intracoronary administration.

Treatment of arterial stenoses by the Simpson atherectomy catheter is carried out by resecting the atheroma. A rotating cutter housed in a cylindrical chamber with a lateral opening is applied against the arterial wall by a low-pressure balloon. Several cuts are made until a large enough diameter of arterial lumen is obtained. We report the results in the first 6 patients treated by this technique using 7F and 9F catheters. All had short (less than 2 cm) and narrow (greater than or equal to 70%) stenoses of iliac, superficial femoral or popliteal arteries. To reduce the stenoses to 30% or less, 4 to 11 cuts were necessary. Histological study of the fragments was performed. The result was inadequate in the only case of stenotic iliac artery and we proceeded with balloon dilatation. The small fragments obtained in this particular case were very hard and calcified. 4 patients with claudication (superficial femoral or popliteal stenosis) were asymptomatic after treatment, whereas one patient suffering from Burger's disease with acral necrotic lesions did not benefit from the procedure in spite of a good morphological result. No complication was encountered. This efficient technique is especially indicated in short segmental stenoses of femoro-popliteal or possibly iliac arteries. It avoids the usual intimal cracks associated with balloon angioplasty and produces a smooth surface whose long term benefit has still to be demonstrated.

Human factor VIII has been dissociated into fragment VIII-C and fragment VIII-AG in the presence of calcium chloride (0.25 M). After removing the calcium, recombination of the molecule is obtained. Fragment VIII-C can be activated by thrombin in a similar manner to the coagulant activity of whole factor VIII. This activation is calcium-dependent. In rabbits immunized against purified F VIII, VIII-C and VIII-AG specific antisera against these three entities were obtained.

The case is reported of a 44-year-old patient without cardiovascular risk factors who complained of typical intermittent claudication. Arteriography and echography led to the diagnosis of cystic adventitial disease of the popliteal artery. Percutaneous puncture under CT control was unsuccessful and surgical resection of the cystic formation was performed. This rare etiology is discussed in relation to the differential diagnosis of intermittent claudication, with particular reference to young patients.

We report a case of acute thrombosis of the common femoral artery which occurred on the tenth day of postoperative prophylactic heparin therapy. Platelet count was 14,000/mm3 at the time of the acute event. Cessation of heparin administration resulted in progressive normalization of the platelet count. Iliofemoral thrombectomy, followed by popliteal thromboembolectomy, allowed successful recanalization of the occluded arteries, after failure of local thrombolysis with low-dose streptokinase. The pathogenesis, diagnosis and treatment of heparin-induced thrombocytopenia associated with thromboembolic complications are discussed.